Vol 70, No 6 (2015)

Aim: to study the process of proteins transamination in syncytiotrophoblast of placenta villi of women who suffered the acute form of cytomegalovirus (CMV) infection during pregnancy.

Methods: 30 pregnant women with CMV infection recurrence at the 25–28th week of pregnancy were examined. The activity of γ-glutamyltransferase in the peripheral blood of pregnant women was determined by spectrophotometry at the device «Stat-Fax-2100» (The USA). Hsp-70 and caspase-3 in placenta homogenate were found out with serological methods. The activity of glutamatdehydrogenase and pyridoxal-5-phosphatase was studied with histochemical method of Z. Loyd at the placenta slice of parturient women. The apoptotic changes in syncytiotrophoblast nuclei were defined by ISEL-method.

Results. The peripheral blood of CMV-seropositive parturient women showed a reduction of γ-glutamyltransferase in 1.30 times. Histochemically we identified the reduction of reaction products' concentration in response to pyridoxal-5-phosphate by 2.14 times, to glutamatdehydrogenase by 1,57 times. At the same time there was an increase of caspase-3 in 2,8 times and reduction of Hsp70 in 2.6 times in placenta homogenate. The number of apoptotic changes in syncytiotrophoblast nuclei increased by 4 times.

Conclusion. Worsening of CMV infection in the period 25–28 weeks of pregnancy leads to disruption of amino acid metabolism in the placenta, causing structural and functional and metabolic adjustment, and is one of the reasons for slow growth and lack of development of the fetus. 

Aims: Determination of operating characteristics of the test based on blood plasma redox potential monitoring in patients with different pathological conditions associated with impaired oxygen metabolism during treatment in postoperative period and expanding the range of parameters of the developed method of investigation of blood plasma redox potential.

Methods: It were examined healthy volunteers group as following group (n =63), groups of patients with transplanted liver (n =64), kidney (n =59), and lungs (n =7). Redox potential measurements were done by platinum electrode, reference electrode was silver-chlorine one. Potentiostate IPC-ProL was used to registrate and record a dependence redox potential via time. Time of measurement was 15 min.

Results: statistically significant differencees of redox potentials ranges was found in healthy volunteers and patients with transplanted kidney and liver. Ratio of measured redox potentials coincident with the values within the confidence interval in healthy volunteers was 12% in patients with transplanted kidney and 10% in patients with transplanted liver. We observed significant differences in the nature of changes of blood plasma's redox potential values in course of monitoring of subgroups of patients with and without complications after liver transplantation. It was found that sensitivity of electrochemical method was 85%, selectivity — 69,8%, precision — 85,2%.

Conclusion: we discovered value ranges of blood plasma redox potential typical for different pathological states; we detected an interaction between the effect of treatment and quantitative changes in the values of the blood plasma redox potentials; criterion for early predicition of complications in patients with transplanted liver was proposed basing on redox potential monitoring during postoperative period.

Objective: to study immunophenotype and NAD- and NAD(P)-dependent dehydrogenase of blood lymphocytes activity indicators in children with hypertrophy of the pharyngeal tonsils (HPT).

Methods: 57 children aged 1–3 years with HPT were examined. The focus group included 35 healthy children of the similar age. The number of СD3+-, СD4+-, СD8+-, СD16+/56+-, СD19+-cells in the blood was determined by flow cytometry. The activity of NAD(P)-dependent dehydrogenase was studied by the method of A. Savchenko and coauth. (1989).

Results: The changes of immunophenotypic spectrum of peripheral blood lymphocytes in infants with HPT have been revealed. The increase of ribose-5-phosphate and NADN-dependent reactions of macromolecular synthesis, the reduction of malataspartat shunt role in cell energy, the reduction of anaerobic lactate dehydrogenase reaction, the compensatory increase in the glycerol-3-phosphate dehydrogenase activity, the high substrate flow of the citric acid cycle and the reduced level of glutathione have been fixed. The correlation analysis has showed increase in the number of correlations between indicators of investigated oxidoreductase activity in blood lymphocytes in children with HPT and the high level of correlation between the metabolic reactions of the mitochondrial compartment.

Conclusion: the change of immunophenotype, enzymatic activity, correlation pattern of connection between intracellular enzymes of peripheral blood lymphocytes have been revealed in children aged 1–3 years with HPT.

Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptor signaling pathways and cascade of reactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT. These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects the formation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

With the aim to assess the mechanisms of the structural dysfunctions associated with xenograft tissue calcification, we investigated the cellular composition of the explanted xenoaortic epoxy-treated bioprosthetic heart valves. In the leaflets, we revealed multiple cells with retained internal structure. Most of them located on the leaflet surface, at the areas of collagen destruction, and near calcium deposits. Monocytes were the predominant cell fraction on the leaflet surface whilst immune (macrophages, multinucleated giant cells, plasma cells, neutrophils) and connective tissue (fibroblasts, fibrocytes, endothelial, and smooth muscle cells) cells prevailed at the areas of collagen destruction and near calcium deposits. Calcification of the leaflets was accompanied by cellular infiltration, therefore suggesting that pathological mineralization may be associated with cell-mediated processes.

Backgraund: The result of comparative study of oropharyngeal microbiota taxonomic composition in patients with different severity level of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is presented in this paper. 

Aims: To compare oropharyngeal microbiota composition in case of bronchial asthma and chronic obstructive pulmonary disease in different severity levels. 

Metods: 138 patients, 50 with BA and 88 with COPD were studied. For each patient was collected anamnesis vitae, swab from the back of the throat and performed physical examination. High-throughput 16S ribosomal RNA gene sequencing and bioinformatic analysis was employed to characterize the microbial communities. 

Results: As a result of the study was found a number of differences on various taxonomic levels in microbiota’s composition within group of patients with different severity level of BA and group of patients with different severity level of COPD and between those groups. COPD patients with GOLD 1–2 in comparison with GOLD 3–4 patiens are marked by prevalence of species Brevibacterium aureum, genus Scardovia, Coprococcus, Haemophilus, Moryella, Dialister, Paludibacter and decrease of Prevotella melaninogenica species. BA patients with severe uncontrolled asthma in comparison with patients which have mild persistent asthma are marked by decrease of Prevotella and increase of species Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis and genus Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas, Sneathia. Patient’s microbiota in BA group in comparison with COPD group is characterized by the prevalence of Prevotella melaninogenica and genus Selenomonas, Granulicatella и Gemella, and decrease of Prevotella nigrescens, Haemophilus influenza and genus Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus и Sediminibacterium. There are no differences between microbiota composition in case of severe uncontrolled BA and very severe COPD. 

Conclusion: Lack of differences in oropharyngeal microbiota taxonomic composition between patients with severe uncontrolled BA and very severe COPD allow us to suggest a similarity of bronchopulmonary system condition in case of diseases' severe stages.

The process of tumor progression is closely related to the intracellular, extracellular and intramembranous proteolysis. Many studies indicate that the proteases function as part of an extensive multidirectional network of proteolytic interactions. Disturbance of strictly controlled equilibrium of the proteolytic system is described in a number of diseases, including cancer. The paper presents a review of the available data concerning the contribution of intracellular, extracellular and intramembrane proteolysis to the process of squamous cell head and neck carcinoma. Specific mechanisms of interaction of different proteolytic systems in cancer progression both in general and in squamous cell head and neck carcinoma remain underinvestigated. The versatility of functions and complexity of the relationships between proteolytic systems highlights the importance of studying the participation of all degradome components in tumor progression that may clarify the multi-link complex mechanisms of carcinogenesis of squamous cell head and neck carcinoma and to identify markers of progression and/or a targets for therapeutic intervention.

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RAGE are well-known: advanced glycation end products (AGE), amyloid-beta (Аβ), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 и S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.

The review represents the problems of a damage to the vital organs in newborns with the Abdominal Compartment Syndrome (ACS). Particular attention is paid to the key predisposing factors and key links of the renal damage’s pathogenesis in newborns with ACS. This review presents the latest data about the role of the hypoxia at the initiation of damage of the renal parenchyma, the prospects for the use of various molecular markers for early diagnostics of nephropathy. Creation of molecular cell test system for the diagnostics and monitoring of renal damage in newborns with ACS is a promising trend in the treatment and prevention nephropathy in newborns.

The review is devoted to the mechanism of duodenal motility activation caused by sympathetic nerves. The authors have found that stimulation of the sympathetic trunk in the thoracic cavity in dogs in most cases provide not inhibitory but excitatory motor responses of the duodenum. Excitatory effects were eliminated during 5HT-receptors blockade by promedol and lysergol. Analysis of publications showed that sympathetic trunk contains serotoninergic fibers, providing excitatory motor responses of the duodenum to electrical nerve stimulation. According to histochemical and physiological studies, amount of serotonergic fibers in the sympathetic trunk is several times more than the adrenergic. This means that the body has sertoninergic nerves. Serotoninergic nerve as well as the sympathetic is a collective notion. There are: sympathetic trunks, their ramifications and branches that innervate the internal organs. Since promedol blocks serotonergic nerves, this is plausible cause of constipation in patients after surgical treatment along with the application of this drug.

The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The presence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymus peptides and/or cytokines, controlled by them, enter the brain and exert influence on neuronal function, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.

Backgraund. WHO considers the problem of antimicrobial resistance to be the serious threat to humanity. One approach to solve it is to restrict the use of antimicrobials. This approach implies the implementation of educational programs. Such programmes take much time and money. However, the effectiveness of educational programs is not clear. 

Aims: determine the effectiveness of educational activities in the field of rationalization of the use of antibacterial drugs. 

Materials and methods. Two-stage multicenter research on the practice of antibacterial drugs application and the effectiveness of educational programs designed to rationalize antibiotic therapy in Primorsky Territory. 

Results. It was found that programs aimed only at the training of doctors are ineffective. The frequency of unjustified use of antimicrobials remains high — 72.7% (2002−2003) and 70.4% (2011−2012). 

Conclusion. To improve the rationality of medical prescriptions (antibacterial drugs) it is necessary to combine educational programs with management measures.

 

High morbidity rate of atopic diseases among children, including high importance of grass pollen as a sensitizing agent, determine the relevance of studies on diagnostic examination systems for appointment of adequate therapy. The research of the most relevant allergens for patients to exclude of duplicating and uninformative tests became urgent after development of a new type of diagnostic tests that does not require expensive equipment. 

The objective of this research was to evaluate the results of in vitro- and in vivo-diagnostic examinations of children with various forms of atopic disease caused by pollen of meadow grasses, and to choose the most significant prognostic parameters for the diagnosis. 

Methods: 277 children aged 4–16 years with various forms of atopic disease were included in the study. There were performed skin prick tests and determination of IgE-antibodies levels to allergen extracts of cocksfoot (g3), meadow fescue (g4), timothy grass (g6). 

Results: In the studied group of patients 32–50% of children have antibodies to grass allergens. There was a close correlation of antibody response on the investigated allergens, quantitative coincidence of IgE-antibodies to g3 and g4 allergens levels. IgE (g6) concentration was close to the IgE(g3) and IgE(g4) levels (85,0±21,6%). Analysis of the skin tests results showed that 44% of patients have a positive response to grass allergens, and in vivo-tests results coincide with serological tests results, mostly in a qualitative sense. The most significant relationship was noted between in vivo and in vitro-tests in the results of testing the response to meadow fescue pollen.

Conclusion: Based on these data IgE concentration index to meadow fescue allergens can be used as a prognostic marker to determine the sensitization of patients with different nosology forms of allergy and can help to improve allergic diagnostics.